Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group.

PURPOSE: The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS.

PATIENTS AND METHODS: Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration.

RESULTS: In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up.

CONCLUSION: When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.